CELL BIOLOGY PROGRAM PROJECT SUMMARY Cancer is commonly referred to as a ?cell biological problem? in which genetic abnormalities or environmental insults induce profound changes in basic cellular functions such as gene regulation, cell division, cell adhesion, receptor signaling and trafficking, and differentiation. The central goal of the Mayo Clinic Cancer Center (MCCC) Cell Biology Program is to define the molecular genetic and cellular basis of neoplastic transformation, growth, and metastasis while providing insights into cell growth and senescence, organ development, chromatin dynamics, and genomic alterations. The MCCC Cell Biology Program includes 34 members from 16 different departments that collectively bring in substantial cancer-based NIH funding ($4.5M directs with 56% from the NCI). These members conduct research across a broad spectrum of cancers, which is focused in 4 specific aims: 1) To investigate the fundamental genetic and epigenetic mechanisms regulating the cell cycle and transcription control in normal, senescent, and neoplastic cells; 2) To elucidate the mechanisms through which cell signaling pathways and receptor endocytic activity promote uncontrolled cell growth; 3) To determine how the crosstalk between cancer cells and their microenvironment promotes cancer growth by regulating neo-angiogenesis, inflammation, immune evasion, and fibrosis; and 4) To understand how cells attach to substrates and to each other, and how these attachments are altered as a cell initiates migration and invasion. The Cell Biology Program studies cellular processes relevant to the development or prevention of a broad spectrum of human cancers and broadly interfaces with other MCCC Programs. In addition to conducting innovative and cutting-edge cancer-relevant research, the Cell Biology Program organizes and sponsors many interactive scientific gatherings, including national and international meetings, and provides a central hub for basic cancer biology at Mayo Clinic. Of the 483 cancer-relevant papers published by our members between 2013 and 2017, 66 were intraprogrammatic and 235 were interprogrammatic, underscoring the high value added by the Program to the Cancer Center.